Abstract
The effect of the antidepressant fluoxetine on Ca2+ signaling in cultured cells was largely unknown. The effect of various concentrations of fluoxetine on [Ca2+]i in populations of bladder female transitional cancer (BFTC) cells was evaluated by using fura-2 as a Ca2+ probe. Fluoxetine increased [Ca2+]i concentration dependently (20-100 μM) with an EC50 value of 30 μM. The response was inhibited by 50-60% on extracellular Ca2+ removal. In CA2+-free medium, pretreatment with 1 μM thapsigargin (an inhibitor of the endoplasmic reticulum Ca2+ pump) abolished 50 μM fluoxetine-induced Ca2+ release; whereas pretreatment with fluoxetine did not alter the thapsigargin-induced Ca2+ response. Addition of 3 mM Ca2+ increased [Ca2+]i after pretreatment with 50 μM fluoxetine in Ca2+-free medium, suggestive of fluoxetine-induced capacitative Ca2+ entry. Suppression of inositol 1,4,5-trisphosphate formation by 2 μM U73122 (a phospholipase C inhibitor) did not affect 50 μM fluoxetine-induced Ca2+ release. Collectively, this study shows that fluoxetine increased [Ca2+]i in bladder cancer cells in a concentration-dependent fashion, by releasing Ca2+ from thapsigargin-sensitive Ca2+ stores in an IP3-independent manner, and by inducing Ca2+ influx from extracellular medium.
Original language | English |
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Pages (from-to) | 503-507 |
Number of pages | 5 |
Journal | Pharmacological Research |
Volume | 43 |
Issue number | 5 |
DOIs | |
State | Published - 2001 |
Externally published | Yes |
Keywords
- Antidepressant
- Bladder cancer cells
- Ca
- Fluoxetine
- Fura-2
- Serotonin